This project aims to combine new technologies in mathematical modeling, statistical methods, computer simulations, pharmacokinetics/pharmacodynamics, and clinical/biological sciences in HIV/AIDS research to develop simulation systems for AIDS clinical trials. We expect that the trial simulation systems can help with design of complicated AIDS clinical trials, to optimize sophisticated AIDS treatment strategies, and to study biological mechanisms of HIV infection and AIDS pathogenesis so that new biological hypotheses can be generated for clinical tests. First, mathematical/statistical models will be developed for AIDS clinical trial simulations. These models include drug exposure models for incorporating pharmacokinetics and adherence information, drug sensitivity (resistance) models, drug efficacy and antiviral response models. Statistical methods for estimating model parameters and for making inferences from simulation data will be developed. Based on the established models, computer simulation systems will be developed. Several simulation projects are proposed to test and validate the simulation systems. We expect that the developed AIDS clinical trial simulation systems can be used by AIDS clinicians to design new AIDS clinical trials and to explore new treatment strategies without risking human subjects. AIDS physicians and patients may also use the simulation systems to predict and monitor the outcomes of an antiretroviral treatment. The developed systems will be a useful tool for AIDS clinicians to develop individualized treatments for their patients.